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Pharmacological effects and tissue concentrations of amphetamine in rats pretreated with diethyldithiocarbamate (DDC), a dopamine-β-hydroxylase inhibitor

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Summary

Diethyldithiocarbamate (DDC), 400 mg kg−1,s. c., given 1 hour or 16 hours before administration of (+)-amphetamine sulphate, 4 mg kg−1, i. p., increased the tissue concentrations and reduced the rates of elimination of amphetamine in brain, plasma, lung, kidney and liver, and this was probably due to inhibition of amphetaminep-hydroxylation. Concomitantly, there was a prolongation of two pharmacological effects of the stimulanti. e. hyperthermia and motor hyperactivity, in similarly treated rats. However, a hypothermic effect of DDC itself initially counteracted the hyperthermic response to amphetamine, indicating a dual interaction between the two drugs. The multiple biochemical actions of DDC and similar chemical agents seriously confound the interpretation of the results when using these dopamine (β-hydroxylase inhibitors,e. g. as pharmacological tools in elucidating the mechanism of action of other drugs.

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References

  1. Lewander, T. and Jonsson, J. (1973), Drugs and certain conditions interfering with the metabolism and excretion of amphetamine in the rat.In: Psychopharmacology, sexual disorders and drug abuse. Eds: Ban, T. A., Boissier, J. R., Gessa, G. J.et al., North-Holland Publishing Company, Amsterdam-London and Avicenum, Czechoslovak Medical Press, Prague, p. 625–635.

    Google Scholar 

  2. Lewander, T. (1969), Influence of various psychoactive drugs on thein vivo metabolism ofd-amphetamine in the rat. Europ. J. Pharmacol.,6, 38–44.

    Article  CAS  Google Scholar 

  3. Jonsson, J. and Gunne, L.-M. (1972), Interaction of fenfluramine withd-amphetamine-induced excitatory behaviour and hyperthermia. Europ. J. Pharmacol.,19, 52–55.

    Article  CAS  Google Scholar 

  4. Randrup, A. and Munkvad, I. (1970), Biochemical, anatomical and physiological investigations of stereotyped behaviour induced by amphetamines.In: International Symposium on Amphetamines and Related Compounds. Eds: Costa, E. and Garattini, S. Raven Press, New York, p. 695–713.

    Google Scholar 

  5. Randrup, A. and Scheel-Krüger, J. (1966), Diethyldithiocarbamate and amphetamine stereotype behaviour. J. Pharm. Pharmacol.,18, 752.

    CAS  PubMed  Google Scholar 

  6. D’Encarnacao, P. S., D’Encarnacao, P. and Tapp, J. T. (1969), Potentiation of amphetamine induced psychomotor activity by diethyldithiocarbamate. Arch. int. Pharmacodyn.,182, 186–189.

    PubMed  Google Scholar 

  7. Mayer, O. and Eybl, V. (1971), The effect of diethyldithiocarbamate on amphetamine-induced behaviour in rats. J. Pharm. Pharmacol.,23, 894–896.

    CAS  PubMed  Google Scholar 

  8. Corrodi, H., Fuxe, K., Ljundgahl, A. and Ögren, S.-O. (1970), Studies on the action of some psychoactive drugs on central noradrenaline neurones after inhibition of dopamine-β-hydroxylase. Brain Res.,24, 451–470.

    Article  CAS  PubMed  Google Scholar 

  9. Jonsson, J. and Lewander, T. (1973), Effects of diethyldithiocarbamate and ethanol on thein vivo metabolism and pharmacokinetics of amphetamine in the rat. J. Pharm. Pharmacol.,25, 589–591.

    CAS  PubMed  Google Scholar 

  10. Jonsson, J. and Lewander, T. (1974), Effects of the dopamine-β-hydroxylase inhibitor FLA 63 on the kinetics of elimination of amphetamine in the rat. J. Pharm. Pharmacol.,26, 907–909.

    CAS  PubMed  Google Scholar 

  11. Lai, S., Sourkes, P. L. and Missala, K. (1974), The effect of certain tranquilizers, chlorpromazine metabolites and diethyldithiocarbamate on tissue amphetamine levels in the rat. Arch. int. Pharmacodyn.,207, 122–130.

    Google Scholar 

  12. Maickel, R. P., Cox, R. H. Jr., Miller, F. P., Segal, D. S. and Russel, R. W. (1969), Correlation of brain levels of drugs with behavioural effects. J. Pharmacol, exp. Ther.,165, 216–224.

    CAS  Google Scholar 

  13. Lewander, T. (1971), On the presence ofp-hydroxyno-rephedrine in the rat brain and heart in relation to changes in catecholamine levels after administration of amphetamine. Acta Pharmacol, toxicol. (Kbh.),29, 33–48.

    CAS  Google Scholar 

  14. Jonsson, J. (1976), Influence of various drugs on the metabolism of amphetamine in rat liver microsomes and perfused liver preparations. Submitted for publication.

  15. Pfeifer, A. K., Galambos, E. and Gyorgy, L. (1966), Some central nervous properties of diethyldithiocarbamate. J. Pharm. Pharmacol.,18, 254.

    CAS  PubMed  Google Scholar 

  16. Strömme, J. H. (1965), Metabolism of disulfiram and diethyldithiocarbamate in rats with demonstration of anin vivo ethanol induced inhibition of the glucuronic acid conjugation of the thiol. Biochem. Pharmacol.,14, 391–408.

    Google Scholar 

  17. Thorne, G. D. and Ludwig, R. A. (1962), The dithiocarbamates and related compounds, Elsevier, Amsterdam-New York.

    Google Scholar 

  18. Olesen, O. V. (1966), Disulfiram (AntabuseR) as inhibitor of phenytoin metabolism. Acta Pharmacol, toxicol. (Kbh.),24, 1075–1080.

    Google Scholar 

  19. Stripp, B., Greene, F. E. and Gillette, J. R. (1969), Disulfiram impairment of drug metabolism by rat liver microsomes. J. Pharmacol, exp. Ther.,170, 347–354.

    CAS  Google Scholar 

  20. Deitrich, R. A. and Erwin, V. G. (1971), Mechanism of the inhibition of aldehyde dehydrogenasein vivo by disulfiram and diethyldithiocarbamate. Molec. Pharmacol.,7, 301–307.

    CAS  Google Scholar 

  21. Vesell, E. S., Passanonti, G. T. and Lee, C. H. (1971), Impairment of drug metabolism by disulfiram in man. Clin. Pharmacol, and Ther.,12, 758–792.

    Google Scholar 

  22. Notten, W. R. F. and Hendersson, T. Th. (1973), Effect of disulfiram on the urinaryd-glucaric acid excretion and activity of some enzymes involved in drug metabolism in guinea pig. Arch. int. Pharmacodyn.,205, 199–208.

    CAS  PubMed  Google Scholar 

  23. Goldstein, N., Anagnoste, B., Lauber, E. and McKereglan, M. R. (1964), Inhibition of dopamine-β-hydroxylase by disulfiram. Life sci.,3, 163–167.

    Article  Google Scholar 

  24. Musacchio, J. M., Kopin, I. J. and Snyder, H. S. (1964), Effects of disulfiram on tissue norepinephrine content and subcellular distribution of dopamine, tyramine and their β-hydroxylated metabolites. Life Sci.,3, 769–775.

    Article  CAS  PubMed  Google Scholar 

  25. Collins, G. G. S. (1965), Inhibition of dopamines-β-oxydase by diehtyldithiocarbamate. J. Pharm. Pharmacol.,17, 526–527.

    CAS  PubMed  Google Scholar 

  26. Hashimoto, Y., Ohi, Y. and Imaizumi, R. (1965), Inhibition of brain dopamine-β-oxidasein vivo by disulfiram. Jap. J. Pharmacol.,15, 123–124.

    Google Scholar 

  27. Thoenen, H., Haefely, W., Gey, K. F. and Hürlimann, A. (1965), Diminished effects of symphatetic nerve stimulation in cats pretreated with disulfiram: Liberation of dopamine as sympathetic transmitter. Life Sci.,4, 2033–2038.

    Article  CAS  PubMed  Google Scholar 

  28. Carlsson, A., Lindkvist, M., Fuxe, K. and Hökfelt, T. (1966), Histochemical and biochemical effects of diethyldithiocarbamate on tissue catecholamines. J. Pharm. Pharmacol.,18, 60–62.

    CAS  PubMed  Google Scholar 

  29. Musacchio, J. M., Goldstein, M., Anagnoste, B., Poch, G. and Kopin, I. J. (1966), Inhibition of dopamines-β-hydroxylase by disulfiramin vivo. J. Pharmacol, exp. Ther.,152, 56–61.

    CAS  Google Scholar 

  30. Carlsson, A., Fuxe, K., Hökfelt, T. (1967), Failure of dopamine to accumulate in central noradrenaline neurons after depletion with diethyldithiocarbamate. J. Pharm. Pharmacol.,19, 481–483.

    CAS  PubMed  Google Scholar 

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  1. Psychiatric Research Center, University of Uppsala, Ulleräker Hospital, 75017, Upssala, Sweden

    J. Jonsson & T. Lewander M.D.

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  1. J. Jonsson
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  2. T. Lewander M.D.
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Jonsson, J., Lewander, T. Pharmacological effects and tissue concentrations of amphetamine in rats pretreated with diethyldithiocarbamate (DDC), a dopamine-β-hydroxylase inhibitor. European Journal of Drug Metabolism and Pharmacokinetics 1, 161–166 (1976). https://doi.org/10.1007/BF03189271

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  • DOI: https://doi.org/10.1007/BF03189271

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